Orville adalbert dapert-sensel-timmeb



l cine UNITED STATES ORVILLE ADALBL'ET DAFERT-SENSEL-TlZMMEJ/R. OLEVIENNA, AUSTBIA.

MEDICAL COMPOUND AND PRDCESS EOE, BIANUFACTURING THE SAIVIE.

No Drawing.

To all whom it may concern:

Be it known that I, ORvILLE Aux-sinner 5 Austriahave invented a certainnew and useful Medical Compound and Process for lllanufacturing theSame, of which the following is a specification.

This invention relates. to a new mediin which the medicinal effect ofquinine is combined with that of arsenic, which combination has beendesired for a long time. I have discovered, that upon treating quinineor its salts with halogen compounds of arsenic, I can produce newcompounds which have the two effects above noted, and which areparticularly effective in coinbatting diseases caused by organismshaving entered the blood. These medicines may be administered byintravenous or intramuscular injection.

The reaction between the quinine and the arsenic compound can be carriedout under certain conditions in order to yield a reaction product whichmay be easily isolated in a pure state. "When solid quinine bases aretreated with an excess of trichlo ride of arsenic the temperature risesand a gummy substance is obtained which can be crystallized only withdiiliculty. Experiments have shown that the reaction must be broughtabout in an inert reaction veiicle which is a solvent for the startingmaterials, in order to avoid the difficulty of severalrecrystallizations. A suitable reaction vehicle is for instancechloroform, which easily dissolves the original materials, while thereaction product being insoluble therein, is precipitated. By workingwith the said liquid I obtain wellformed crystals readily soluble inwater, without danger of decomposition; this allows of an eas dosage andmanipulation of the new medicine. By altering the proportions of thecomponents or the temperature of the reaction the amount of quinine andof the halogen compound of arsenic entering into the final product maybe varied. if quinine salts or different quinine bases are used, aseries of new compounds of similar properties may be obtained. In

all these compounds, arsenic is not present as ionizable arsenic.

Ewamplc grams of trichloride of arsenic dissolved in 200 grams ofchl0roform are poured into a solution of 5 grams Application filedDecember 15, 1924.

Serial No. 756,061.

of anhydrous quinine hydrochloride in 150 grains of chloroform, themixture being preferably stirred and care being taken that thetemperature does not rise above 10 C. A crystal pulp is gradually formedwhich contains fine needles in chloroform, which is allowed tc stand for24 hours to allow completion of the separation from the mother liquor.The crystal pulp is then washed on a filter flask or the like withchloroform and then freed from the main portion of the obstinatelyadhering chloroform by drying in vacuo and finally by drying in a dryingoven at 100 C. If the mass is not stirred during the precipitation,formation of spherical agglonierations of crystals may sometimes occur.

The product is highly hygroscopic, and decomposes without melting atabove 100 C. The compound is slightly soluble in chloroform, but readilysoluble in water and soluble in ethyl and methyl alcohol. The analysiswhich corresponds with the determination of toxic efficiency, shows amolecular ratio of hydrochloride of quinine to arsenic trichloride of1:1, if the above noted quantities are used, and above noted temperatureconditions followed.

The results of the analysis are as fol lows:

As Cl N C H 13. 83 26. 17 5.17 44;. 28 4. 65 calculated. 13. 80 26.075.09 44. 19 4.79 found.

13.72 26.10 5.11 44.15 4. 83 found.

From these figures, I believe the formula to be C H O H AsCl Example 2.-lhe solutions of the starting materials are prepared as described in Ereample 1 and are allowed to react at 25 to C. If the further treatment isaccording to Example 1 the resulting compounds are water soluble. In amodified form of execution, the molecular ratio of quinine hydrochlorideto arsenic chlorid may be 1:1 or 2:1 or 3:1 or 4:1. The compoundsproduced when using such ratios, also may be dosed in accordance withtheir arsenic contents and are very suitable for thera peutic use.

Example 5.By working with the free base, quinine, instead of thecorresponding amount of quinine hydrochloride as stated in Examples 1and 2, or with other quinine ioiinsianee chiuidine or if desired with a(lilier-ent halogen compound of areenic for ii'istance arsenictrifluoricle,

similar new compounds are obtained.

As above stated, quinine, its sails such as li :(lri'ielilorinieiniinine bases (e. cliinii ine) can be employed, i refer to this classerials liereinaiii'e", under the expresrion a quinine coingouucl.

What 1 elaini is:

A. iii-(wees: \i'iiieli comprises rezioting i lniliiie oi" arsie a ienquinine conii nd thereof.

A comp; see reacting o; arsenic upon a quinine dissolved. in an or- 1 oform a double lie compo mnipou (t Y process which Qi liiDllSQS reacting\ililll a halide of arsenic upon a quinine eonipounii iJOi'il beingl2SEOlVQ l 1n UlliOl'O- form, to form a double compound inereoi.

4?. process which connorisei reacting an a halide o2 arsenic upon aquinine eonipounil \YllllL not above 16 C., to ioi'iii a ilnziliieeon'ipound thereof.

no la. process which comprises reacting .ill'li an 211" Q111' (lllOlMlCupon a quinine compound lo form a double compound illne la soluble inWater but notcil fiifi' fllih and cons ti oi a halide of .1 a newformula 1-1 In iestinnmy \i signature.

a cini'ipo ini'l of 'Cl hereunto :ili'iz;

ORVELLE ADALBERT DAFERT-SENSEL-TIMMER.

